瑞芬太尼预处理对大鼠离体心脏缺血再灌注损伤的保护作用

目的KATP通道在瑞芬太尼预处理对大鼠离体心脏缺血再灌注损伤保护作用中的角 色。方法 雄性SD大鼠48只,体重200～250 g,建立Langendorff大鼠离体心脏模型,随机分为6组: 每组8只。缺血再灌注组(I／R组):缺血前用Krebs-Ringer灌注液持续灌注45 min;瑞芬太尼预处理组 (RPC组):缺血前用含100μg／L瑞芬太尼的灌注液灌注5 min,停5 min,共3次。HMR RPC、5-HD RPC组分别用含1×10-4mol／L肌浆网KATP(sac-KATP)通道阻断剂HMR-1098、1×10-5mol／L线粒体KATP (mito-KATP)通道阻断剂5-羟基葵酸盐(5-HD)与上述浓度的瑞芬太尼混合液的灌注液灌注,时间从瑞 芬太尼预处理前10 min至瑞芬太尼预处理后5 min(共计45 min)。HMR、5-HD组分别在缺血前用含有 上述两种KATP通道阻断剂的灌注液灌注45 min。测定心脏稳定15 min(基础值)、缺血前即刻、缺血30 min、再灌注120 min时冠脉流量(CF);测定再灌注5、10 min时冠脉流液中乳酸脱氢酶(LDH)活性;再灌 注120 min时处死大鼠,计算心肌缺血梗死区(IS)体积及IS面积与缺血危险区面积比值(IS/AAR)。结 果 与I／R组比较,RPC、HMR RPC组IS体积和IS／AAR降低,RPC组在再灌注5、10 min时LDH活性 降低(P<0．01);5-HD RPC、HMR和5-HD组IS体积和IS／AAR差异无统计学意义(P>0．05)。与 RPC组比较,5-HD RPC、HMR和5-HD组IS体积和IS／AAR增大,5-HD RPC、HMR和5-HD组在再灌 注5、10 min时LDH活性升高(P<0．01)。与基础值相比,RPC组缺血前即刻CF增高,HMR RPC组降 低(P<0．05或0．01)。结论 通过激活心脏mito-KATP通道瑞芬太尼预处理对大鼠离体心脏缺血再灌 注损伤有一定的保护作用。     

c-Jun氨基末端激酶在瑞芬太尼预处理减轻大鼠心肌缺血再灌注损伤中的作用

目的 评价c-Jun氨基末端激酶(JNK)在瑞芬太尼预处理(RPC)减轻大鼠心肌缺血再灌注损伤中的作用.方法 成年雄性SD大鼠126只,体重300-350 g,随机分为5组:缺血再灌注组(I/R组)(n=38)、缺血预处理组(IPC组)(m=38)、RPC组(n=38)、SP+IPC组(n=6)和SP+RPC组(n=6).采用结扎左冠状动脉30 min再灌注120 min的方法制备心肌缺血再灌注模型.IPC组在缺血前30min行IPC:缺血5 min,再灌注5 min,重复3次;RPC组在缺血前30 min 行RPC:静脉输注瑞芬太尼6 ug·kg-1·min-1 5 min,停止5 min,重复3次;SP+RPC组和SP+IPC组分别于RPC或IPC前5 min腹腔注射JNK选择性阻滞剂SP600125 6 mg/kg.I/R组、IPC组和RPC组于缺血前即刻、缺血5.30 min和再灌注5、30、60 min时随机处死5只大鼠,测定左心室磷酸化JNK(p-JNK)的表达.于再灌注末处死其余大鼠,取心肌,计算左心室(LV)与右心室(RV)体积之和(LV+RV)、梗死区(IS)面积占缺血危险区(AAR)面积的百分比(IS/AAR).结果 与I/R组相比,IPC组和RPC组IS/AAR降低(P＜0.01),SP+PRC组和SP+IPC组IS/AAR差异无统计学意义(P＞0.05);缺血前即刻IPC组心肌p-JNK表达增加,缺血5min时RPC组和IPC组心肌p-JNK表达均降低,再灌注期间RPC组和IPC组心肌p-JNK表达均增加(P＜0.01).结论 JNK参与了瑞芬太尼预处理减轻大鼠心肌缺血再灌注损伤.     

糖尿病因素对舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤的影响

目的 探讨糖尿病因素对舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤的影响.方法 健康成年雄性SD大鼠,体重250～300 g,采用腹腔注射链脲佐菌素50 mg/kg的方法制备糖尿病模型.取造模成功的大鼠30只,采用随机数字表法,将其随机分为3组(n＝10):糖尿病假手术组(DM-S组)、糖尿病缺血再灌注组(DM-IR组)和糖尿病舒芬太尼后处理组(DM-SP组).另取正常大鼠30只,采用随机数字表法,将其随机分为3组(n=10):非糖尿病假手术组(NDM-S组)、非糖尿病缺血再灌注组(NDM-IR组)和非糖尿病舒芬太尼后处理组(NDM-SP组).采用结扎左冠状动脉前降支30 min后再灌注的方法制备心肌缺血再灌注模型.SP组于再灌注前5 min经颈静脉注射舒芬太尼1.0 μg/kg.于缺血前、缺血30 min和再灌注120 min时记录MAP、SBP和HR,计算收缩压心率乘积(RPP).再灌注120 min时取血样,测定血浆cTnI浓度,处死大鼠后,取心脏,测定左右心室体积之和、缺血危险区体积(AAR)和梗死区体积(IS),计算IS/AAR.结果 非糖尿病和糖尿病大鼠心肌缺血再灌注时MAP、RPP降低,血浆cTnI浓度升高,心肌发生梗死样改变.舒芬太尼后处理可降低非糖尿病大鼠心肌缺血再灌注时IS、IS/ARR和血浆cTnI浓度,对糖尿病大鼠心肌缺血再灌注时各指标无明显影响.DM-SP组IS、IS/ARR和血浆cTnI浓度明显高于NDM-SP组(P＜0.05).结论 糖尿病因素可消除舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤的作用.     

诱导型一氧化氮合酶在舒芬太尼预处理减轻大鼠心肌缺血再灌注损伤中的作用

目的 探讨诱导型一氧化氮合酶(iNOS)在舒芬太尼预处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 成年雄性SD大鼠30只,体重250～330 g,采用随机数字表法,将大鼠随机分为5组(n=6):假手术组(S组)只穿线,不结扎;心肌缺血再灌注组(I/R组)采用结扎左冠状动脉前降支30min,再灌注120 min的方法制备大鼠心肌缺血再灌注损伤模型;舒芬太尼预处理组(SF组)缺血前24 h经尾静脉输注舒芬太尼120μg/kg,输注时间30 min;舒芬太尼预处理+iNOS特异性抑制剂S-甲硫脲组(SF+SMT组)缺血前24 h经尾静脉输注舒芬太尼120μg/kg,缺血前10 min静脉注射SMT 10 mg/kg;SMT组缺血前10 min静脉注射SMT 10 mg/kg.于缺血前30 min、缺血30 min、再灌注120 min时记录HR和MAP,计算RPP(SP× HR).于再灌注120 min时取颈动脉血样2 ml,测定血浆NO浓度,随后取心脏制病理切片,测定缺血危险区(AAR)和梗死区(IS)体积,计算心肌梗死体积(IS/AAR),测定心肌iNOS表达.结果 与S组比较,余4组再灌注120 min时MAP和RPP降低,IS/AAR升高,I/R组和SMT组缺血30 min时MAP和RPP降低(P＜0.05);与I/R组比较,SF组、SF+SMT组和SMT组HR、MAP和RPP差异无统计学意义,SF+SMT组和SMT组IS/AAR和血浆NO浓度差异无统计学意义(P＞0.05),SF组IS/AAR降低,血浆NO浓度和心肌iNOS表达升高(P＜0.05).结论 iNOS参与了舒芬太尼预处理减轻大鼠心肌缺血再灌注损伤的过程.

Abstract：

Objective To investigate the role of inducible nitric oxide synthase (iNOS) in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil preconditioning in rats. Methods Thirty adult male SD rats, weighing 250-330 g, were randomly divided into 5 groups ( n =6 each): sham operation group (group S),I/R group, sufentanil preconditioning group (group SF), sufentanil preconditioning + a specific inhibitor of iNOS S-methyl thiourea (SMT) group (group SF+ SMT) and S-methyl thiourea group (group SMT). In I/R,SF,SF+SMT and SMT groups, myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Group SF received 30 min infusion of sufentanil 120 μg/kg via caudal vein 24 h before ischemia. Group SF + SMT received infusion of sufentanil 120 μg/kg via caudal vein 24 h before ischemia and then SMT 10 mg/kg was injected 10 min before ischemia. In group SMT, SMT 10 mg/kg was injected 10min before ischemia. MAP and HR were recorded at 30 min before ischemia, at 30 min of ischemia and at the end of reperfusion. The rate-pressure product (RPP) was calculated. Arterial blood samples were obtained immediately at the end of reperfusion to determine the plasma concentration of NO. Then the animals were sacrificed and myo cardial tissues were obtained to determine the area at risk (AAR), infarct size (IS) and iNOS expression. IS/AAR was calculated. Results Compared with group S, MAP and RPP were significantly decreased, while IS/AAR was significantly increased at 120 min of reperfusion in the other four groups, and MAP and RPP were significantly decreased at 30 min of ischemia in I/R and SMT groups ( P ＜ 0.05). Compared with group I/R, no significant change was found in HR, MAP and RPP in SF, SF + SMT and SMT groups, and in IS/AAR and plasma NO concentrations in SF + SMT and SMT groups ( P ＞ 0.05), but IS/AAR was significantly decreased, and the plasma NO concentration and iNOS expression were significantly increased in group SF ( P ＜ 0. 05). Conclusion iNOS is involved in reduction of myocardial I/R injury by sufentanil preconditioning in rats.     

COX-2和mito-KATP通道在舒芬太尼预处理对心肌缺血再灌注大鼠延迟性心肌保护中的作用

目的 探讨环氧合酶-2(COX-2)和线粒体ATP敏感性钾通道(mito-KATP通道)在舒芬太尼预处理对心肌缺血再灌注大鼠产生延迟性心肌保护中的作用.方法 健康成年雄性Wistar大鼠72只,体重250～300 g,随机分为6组(n=12),Ⅰ组～Ⅲ组心肌缺血前24 h腹腔注射生理盐水1 ml/kg;Ⅳ组～Ⅵ组心肌缺血前24 h腹腔注射舒芬太尼20μg/kg;Ⅱ组和Ⅴ组心肌缺血前30 min腹腔注射选择性COX-2抑制剂NS-398 5 mg/kg;Ⅲ组和Ⅵ组心肌缺血前10 min经右侧股静脉注射选择性mito-KATP通道阻断剂5-羟葵酸(5-HD)10 mg/ks.各组随机取6只大鼠,于心肌缺血前即刻处死,采用Western blot法检测心肌组织COX-2表达,ELISA法测定心肌组织PGE2及PGF1α含量.各组其余6只大鼠采用结扎左冠状动脉前降支45 min再灌注120 min的方法制备心肌缺血再灌注模型,记录缺血前即刻、缺血15、30、45 rain、再灌注30、60、90、120 min时的HR及MAP,计算二者乘积(RPP);于缺血前即刻、缺血45 nfin及再灌注120 rain时取右颈内动脉血样0.5 ml,测定血浆肌酸激酶同工酶(CK-MB)活性;于再灌注120min时取心脏,测定左心室面积(LV)、缺血危险区面积(AAR)和梗死区面积(LA),计算AAR/LV及IMAAR.结果 各组缺血再灌注期间HR、MAP和RPP逐渐降低,再灌注期间HR、MAP和RPP明显低于基础值(P<0.05),各组间HR、MAP、RPP及AAR/LV比较差异无统计学意义(P>0.05).与Ⅰ组比较,Ⅳ组血浆CK-MB活性降低,LA/AAR降低,心肌COX-2表达上调,PGE2及PGF1α含量升高(P<0.05),Ⅱ组和Ⅲ组血浆CK-MB活性、IA/AAR、心肌COX-2表达、PGE2及PGF1α含量差异无统计学意义(P>0.05);与Ⅳ组比较,Ⅴ组和Ⅵ组血浆CK-MB活性升高,IMAAR升高,Ⅴ组心肌PGE2和PGF1α含量降低(P<0.05),Ⅴ组心肌COX-2表达、Ⅵ组心肌COX-2表达、PGE2及PGF1α含量差异无统计学意义(P>0.05).结论 COX-2和mito-KATP通道共同介导舒芬太尼预处理对心肌缺血再灌注大鼠的延迟性心肌保护作用.     

δ和κ阿片受体介导雷米芬太尼预处理对心脏的保护作用

目的探讨三种阿片受体(OR)在雷米芬太尼预处理对大鼠离体心脏缺血再灌注损伤保护作用中的角色。方法在Langendorff离体心脏模型,随机将64只SD大鼠心脏分为八组:对照组(CON组),雷米芬太尼预处理组(RPC组),Naltrindole组(NTD组,δOR阻断剂),norBinaltorphimine组(norBNI组,κOR阻断剂),CTOP组(μOR阻断剂),NTD RPC、BNI RPC和CTOP RPC组。RPC在缺血前给予浓度为100μg/L的雷米芬太尼5min停用5min,共重复3次。三种阿片受体阻断剂(浓度均为5×10-6mol/L)分别从RPC前10min到缺血后5min给予。观察心肌缺血梗死区(IS/AAR)、冠脉流量(CF)、乳酸脱氢酶(LDH)和HR。结果IS/AAR在RPC组减小(P<0.01),RPC这种作用被NTD和BNI消除:NTD RPC组(52.3±5.2)%,BNI RPC组(43.5±6.0)%(P<0.01);而在CTOP RPC组与RPC组差异无显著意义,与CON组差异有极显著意义(P<0.01)。相似的情况也表现在LDH。结论心脏上的δ和κ受体介导了雷米芬太尼预处理对心脏的保护作用。     

iNOS在瑞芬太尼预处理对大鼠产生延迟性心肌保护效应中的作用

目的 评价诱导型一氧化氮合酶(iNOS)在瑞芬太尼预处理对大鼠产生延迟性心肌保护效应中的作用.方法 成年雄性Wistar大鼠36只,体重250～300 g,采用结扎大鼠左冠状动脉左前降支的方法 建立心肌缺血再灌注模型,缺血30 min,再灌注120 min.随机分为6组(n=6):Ⅰ组、Ⅱ组和Ⅲ组心肌缺血前24 h时尾静脉输注生理盐水0.1 ml·kg-1·min-15 min,重复3次,间隔5 min,Ⅱ组心肌缺血前10 min时尾静脉注射iNOS抑制剂Smethylthiourea(SMT)10 ms/kg,Ⅲ组生理盐水输注结束后尾静脉注射SMT 10 ms/ks.Ⅳ组、Ⅴ组和Ⅵ组心肌缺血前24 h时尾静脉输注瑞芬太尼2 μg·kg-1·min-15 min,重复3次,间隔5 min,Ⅴ组心肌缺血前10 min时尾静脉注射SMT 10 mg/kg,Ⅵ组瑞芬太尼预处理结束后尾静脉注射SMT 10 mg/kg.于心肌缺血前、缺血期每隔15 min、再灌注期每隔30 min记录心率(HR)和平均动脉压(MAP),计算心率血压乘积(RPP).于缺血前即刻、缺血30 min和再灌注120 min时抽取右颈内动脉血样,测定血浆肌酸激酶同工酶(CK-MB)活性;于再灌注120 min时处死大鼠,取心脏,测定左心室面积(LVA)、心肌梗死区面积(IA)和缺血危险区面积(AAR),计算AAR/LVA、IA/LVA和IA/AAR.结果 各组问HR、MAP、RPP和AAR/LVA比较差异无统计学意义(P>0.05).与Ⅰ组、Ⅱ组和Ⅲ组比较,Ⅳ组和Ⅵ组缺血30 min和再灌注120 min时血浆CK-MB活性、IA/LVA和IA/AAR降低(P<0.05);Ⅰ组、Ⅱ组和Ⅲ组血浆CK-MB活性、IA/LVA和IA/AAR比较差异无统计学意义(P>0.05);与Ⅳ组比较,Ⅴ组缺血30 min和再灌注120 min时血浆CK-MB活性、IA/LVA和IA/AAR升高(P<0.05);与Ⅴ组比较,Ⅵ组缺血30 min和再灌注120 min时血浆CK-MB活性、IA/LVA和IA/AAR降低(P<0.05).结论 iNOS是瑞芬太尼预处理对大鼠产生延迟性心肌保护效应的介导因子,而非触发因子.     

不同剂量舒芬太尼预处理对大鼠的延迟性心肌保护作用

目的 评价不同剂量舒芬太尼预处理的延迟性心肌保护作用.方法 成年雄性Wistar大鼠42只,体重250～300 g,随机分为7组(n=6),心肌缺血前24 h,Ⅰ组腹腔注射生理盐水1 ml/kg,Ⅱ组、Ⅲ组、Ⅳ组和Ⅴ组分别腹腔注射舒芬太尼1、5、10、20 μg/kg,Ⅵ组和Ⅶ组分别接受与Ⅴ组、Ⅰ组相同的处理,注射舒芬太尼前15 min均腹腔注射非选择性阿片受体阻断剂纳洛酮1 mg/kg.采用结扎冠状动脉左前降支的方法 建立心肌缺血再灌注模型,缺血45 min,再灌注120 min.于缺血前、缺血期每隔15 min、再灌注期每隔15 min监测心率(HR)和平均动脉压(MAP),计算HR与MAP的乘积(RPP);于缺血前即刻、缺血45 min和再灌注120 min时抽取右颈内动脉血样,测定血清肌酸激酶同工酶(CK-MB)活性;再灌注120 min时取心脏,测定左心室面积(LVA)、心肌梗塞区面积(LA)及缺血危险区面积(AAR),计算AAR/LVA和IA/AAR.结果 与Ⅰ组比较,Ⅲ组再灌注120 min、Ⅳ组和Ⅴ组缺血45 min和再灌注120 min时血清CK-MB活性降低,Ⅲ组、Ⅳ组和Ⅴ组IA/AAR降低(P<0.05);与Ⅱ组比较,Ⅲ组、Ⅳ组和Ⅴ组缺血45 min和再灌注120 min时血清CK-MB活性及IA/AAR均降低(P<0.05);与Ⅲ组比较,Ⅳ组和Ⅴ组缺血45 min和再灌注120 min时血清CK-MB活性及IA/AAR均降低(P<0.05);与Ⅴ组比较,Ⅵ组缺血45 min和再灌注120 min时血清CK-MB活性及IA/AAR均升高(P<0.05);各组AAR/LVA差异无统计学意义(P>0.05).结论 舒芬太尼预处理可通过激活阿片受体对缺血再灌注心肌产生延迟性保护作用,呈剂量依赖性,但具有封顶效应.     

糖尿病因素取消舒芬太尼后处理对大鼠缺血后心肌保护炎症机制的影响

目的研究糖尿病因素取消舒芬太尼后处理对大鼠缺血后心肌保护炎症机制的影响。方法雄性SD大鼠采用腹腔注射链脲佐菌素55mg/kg的方法制备1型糖尿病模型。取健康大鼠和造模成功的1型糖尿病大鼠各30只,随机分为六组(n=10):非糖尿病假手术组(NDM-SHAM组)、非糖尿病缺血-再灌注组(NDM-IR组)、非糖尿病舒芬太尼后处理组(NDM-SP组)、糖尿病假手术组(DM-SHAM组)、糖尿病缺血-再灌注组(DM-IR组)和糖尿病舒芬太尼后处理组(DM-SP组)。结扎冠状动脉左前降支(LAD)30min、再灌注120min,建立大鼠心肌缺血-再灌注损伤模型,舒芬太尼后处理组于再灌注前5min予舒芬太尼1μg/kg股静脉注射。分别记录缺血前即刻、缺血30min和再灌注120min时的HR、MAP的心率收缩压乘积(RPP)。于再灌注120min时计算心肌梗死面积(IS)和检测血浆肌钙蛋白I(cTnI)、TNF-α、IL-6、IL-8和IL-10的浓度。结果与NDM-SHAM组比较,NDM-IR组和NDM-SP组再灌注120min HR明显减慢、缺血30min、再灌注120min MAP和RPP明显降低,血浆cTnI、IL-6、IL-8、IL-10和TNF-α浓度明显升高(P0.05);与DM-SHAM组比较,缺血30min、再灌注120min DM-IR组、DM-SP组MAP和RPP明显降低,血浆cTnI、IL-6、IL-8、IL-10和TNF-α浓度明显升高(P0.05)。与NDM-IR组比较,再灌注120min DM-IR组HR明显减慢,NDM-SP组的IS、IS/AAR明显减少(P0.05),血浆cTnI、IL-6、IL-8和TNF-α浓度明显降低(P0.05),IL-10浓度明显升高(P0.05);与NDM-SP组比较,DM-SP组的IS/AAR明显升高(P0.05),血浆cTnI、IL-6、IL-8和TNF-α浓度明显升高(P0.05),IL-10浓度明显降低(P0.05)。结论炎症机制参与了糖尿病因素取消舒芬太尼后处理对大鼠缺血后心肌保护炎症机制作用。     

不同阿片受体在舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤中的作用

目的 探讨不同阿片受体在舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 健康雄性SD大鼠50只,4～6月龄,体重200 ～ 330 g,采用随机数字表法,将其分为9组,缺血再灌注组(I/R组,n=7)采用结扎左冠状动脉前降支(LAD)30 min、再灌注120 min的方法制备大鼠心肌缺血再灌注损伤模型;缺血后处理组(IPC组,n=7)再灌注前行缺血后处理,进行3个循环的10 s开放LAD 10 s阻断LAD;舒芬太尼后处理组(SP组,n=6)于再灌注前5 min静脉注射舒芬太尼1μg/kg行舒芬太尼后处理;κ受体拮抗剂nor-binaltorphimne+舒芬太尼后处理组(BNI+ SP组,n=5)、δ受体拮抗剂纳曲吲哚+舒芬太尼后处理组(NTD+ SP组,n=5)和μ受体拮抗剂CTOP+舒芬太尼后处理组(CTOP+ SP组,n=5)于舒芬太尼后处理前分别静脉注射BNI 5 mg/kg、纳曲吲哚5 mg/kg和CTOP 1 mg/kg;BNI组、NTD组和CTOP组分别于再灌注前5 min时静脉注射相应剂量BNI、纳曲吲哚和CTOP.于再灌注120 min时采集颈总动脉血样,测定血浆cTnI浓度,处死大鼠后,取心脏,确定心肌梗死(IS)与缺血危险区(AAR)体积的比值(IS/AAR值).结果 与I/R组比较,IPC组、SP组、BNI+ SP组和NTD+ SP组血浆cTnI浓度和IS/AAR值降低(P＜0.05),CTOP+ SP组、NTD组、BNI组和CTOP组血浆cTnI浓度和IS/AAR值差异无统计学意义(P＞0.05);与SP组比较,BNI+ SP组和NTD+ SP组IS/AAR值升高,CTOP+ SP组血浆cTnI浓度和IS/AAR值升高(P＜0.05).结论 μκ和δ阿片受体均介导了舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.